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Identification
Name Chlorpromazine
Accession Number DB00477 (APRD00482)
Type small molecule
Groups approved
Description

The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class, chlorpromazine’s antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts
  • Chlorpromazine hydrochloride
Brand names
Name Company
Chlorpromanyl Technilab (Canada)
Largactil
Thorazine
Brand mixtures Not Available
Categories
  • Antiemetics
  • Antipsychotics
  • Dopamine Antagonists
  • Phenothiazines
  • Antipsychotic Agents
CAS number 50-53-3
Weight Average: 318.864
Monoisotopic: 318.095747015
Chemical Formula C17H19ClN2S
InChI Key InChIKey=ZPEIMTDSQAKGNT-UHFFFAOYSA-N
InChI
InChI=1S/C17H19ClN2S/c1-19(2)10-5-11-20-14-6-3-4-7-16(14)21-17-9-8-13(18)12-15(17)20/h3-4,6-9,12H,5,10-11H2,1-2H3
Plain Text
IUPAC Name
[3-(2-chloro-10H-phenothiazin-10-yl)propyl]dimethylamine
SMILES
CN(C)CCCN1C2=CC=CC=C2SC2=C1C=C(Cl)C=C2
Plain Text
Mass Spec show (8.36 KB)
Taxonomy
Kingdom Organic
Classes
  • Phenothiazines
Substructures
  • Ethers
  • Phenothiazines
  • Aliphatic and Aryl Amines
  • Thiazines
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
Pharmacology
Indication For the treatment of schizophrenia, control nausea and vomiting, For relief of restlessness and apprehension before surgery, adjunct in the treatment of tetanus, control the manifestations of the manic type of manic-depressive illness.
Pharmacodynamics Chlorpromazine is a psychotropic agent indicated for the treatment of schizophrenia. It also exerts sedative and antiemetic activity. Chlorpromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity.
Mechanism of action Chlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects). Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. This action could also account for psychomotor agitation and amplification of psychosis (very rarely noted in clinical use).
Absorption Readily absorbed from the GI tract. Bioavailability varies due to first-pass metabolism by the liver.
Volume of distribution
  • 20 L/kg
Protein binding > 90% to plasma proteins, primarily albumin
Metabolism
Extensively metabolized in the liver and kidneys. It is extensively metabolized by cytochrome P450 isozymes CYP2D6 (major pathway), CYP1A2 and CYP3A4. Approximately 10 to 12 major metabolite have been identified. Hydroxylation at positions 3 and 7 of the phenothiazine nucleus and the N-dimethylaminopropyl side chain undergoes demethylation and is also metabolized to an N-oxide. In urine, 20% of chlopromazine and its metabolites are excreted unconjugated in the urine as unchanged drug, demonomethylchlorpromazine, dedimethylchlorpromazine, their sulfoxide metabolites, and chlorpromazine-N-oxide. The remaining 80% consists of conjugated metabolites, principally O-glucuronides and small amounts of ethereal sulfates of the mono- and dihydroxy-derivatives of chlorpromazine and their sulfoxide metabolites. The major metabolites are the monoglucuronide of N-dedimethylchlorpromazine and 7-hydroxychlorpromazine. Approximately 37% of the administered dose of chlorpromazine is excreted in urine.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Chlorpromazine
hydroxychlorpromazine Details
Chlorpromazine
    		chlorpromazine-N-oxide Details
    Chlorpromazine
      		dedimethylchlorpromazine Details
      Chlorpromazine
        		demonomethylchlorpromazine Details
        Chlorpromazine
          		N-dedimethylchlorpromazine Details
          Route of elimination Kidneys, ~ 37% excreted in urine
          Half life ~ 30 hours
          Clearance Not Available
          Toxicity Agitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, restlessness
          Affected organisms
          • Humans and other mammals
          Pathways Not Available
          Pharmacoeconomics
          Manufacturers
          • Glaxosmithkline
          • Actavis mid atlantic llc
          • Pharmaceutical assoc inc div beach products
          • Wockhardt eu operations (swiss) ag
          • Roxane laboratories inc
          • Sandoz inc
          • Abraxis pharmaceutical products
          • Baxter healthcare corp anesthesia and critical care
          • Marsam pharmaceuticals llc
          • Watson laboratories inc
          • Wyeth ayerst laboratories
          • Alpharma us pharmaceuticals division
          • Abbott laboratories pharmaceutical products div
          • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
          • Kv pharmaceutical co
          • Lederle laboratories div american cyanamid co
          • Purepac pharmaceutical co
          • Private formulations inc
          • Usl pharma inc
          • Vangard laboratories inc div midway medical co
          • West ward pharmaceutical corp
          • Parke davis div warner lambert co
          Packagers
          Dosage forms
          Form Route Strength
          Injection, solution Parenteral 25 mg/ml
          Solution Oral 10 mg/5 ml
          Solution, concentrate Oral 100 mg/ml
          Solution, concentrate Oral 30 mg/ml
          Suppository Rectal 25 mg
          Suppository Rectal 50 mg
          Tablet Oral 10 mg
          Tablet Oral 100 mg
          Tablet Oral 200 mg
          Tablet Oral 25 mg
          Tablet Oral 50 mg
          First Prev Next Last
          Prices
          Unit description Cost Unit
          Chlorpromazine 25 mg/ml amp 8.04 USD ml
          ChlorproMAZINE HCl 200 mg tablet 1.19 USD tablet
          Chlorpromazine 200 mg tablet 1.05 USD tablet
          ChlorproMAZINE HCl 100 mg tablet 0.84 USD tablet
          ChlorproMAZINE HCl 50 mg tablet 0.73 USD tablet
          ChlorproMAZINE HCl 25 mg tablet 0.55 USD tablet
          Chlorpromazine 100 mg tablet 0.39 USD tablet
          ChlorproMAZINE HCl 10 mg tablet 0.37 USD tablet
          Chlorpromazine 10 mg tablet 0.32 USD tablet
          Chlorpromazine 50 mg tablet 0.3 USD tablet
          Chlorpromazine 25 mg tablet 0.17 USD tablet
          First Prev Next Last
          DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
          Patents Not Available
          Properties
          State liquid
          Experimental Properties
          Property Value Source
          melting point < 25 °C PhysProp
          boiling point 200-205 °C at 8.00E-01 mm Hg PhysProp
          water solubility 2.55 mg/L (at 24 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
          logP 5.41 AVDEEF,A (1995)
          logS -5.01 ADME Research, USCD
          Caco2 permeability -4.7 ADME Research, USCD
          pKa 9.3 (at 25 °C) HANSCH,C & LEO,AJ (1985)
          Predicted Properties
          Property Value Source
          water solubility 4.17e-03 g/l ALOGPS
          logP 5.18 ALOGPS
          logP 4.54 ChemAxon
          logS -4.9 ALOGPS
          pKa (strongest basic) 9.2 ChemAxon
          physiological charge 1 ChemAxon
          hydrogen acceptor count 2 ChemAxon
          hydrogen donor count 0 ChemAxon
          polar surface area 6.48 ChemAxon
          rotatable bond count 4 ChemAxon
          refractivity 93.76 ChemAxon
          polarizability 35.1 ChemAxon
          References
          Synthesis Reference Not Available
          General Reference
          1. Leucht S, Wahlbeck K, Hamann J, Kissling W: New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet. 2003 May 10;361(9369):1581-9. Pubmed
          External Links
          Resource Link
          KEGG Drug D00270 Link_out
          KEGG Compound C06906 Link_out
          PubChem Compound 2726 Link_out
          PubChem Substance 46508395 Link_out
          ChemSpider 2625 Link_out
          ChEBI 3647 Link_out
          ChEMBL 3647 Link_out
          Therapeutic Targets Database DAP000374 Link_out
          PharmGKB PA448964 Link_out
          IUPHAR 83 Link_out
          Guide to Pharmacology 83 Link_out
          Drug Product Database 21342 Link_out
          RxList http://www.rxlist.com/cgi/generic3/chlorpromazine.htm Link_out
          Drugs.com http://www.drugs.com/cdi/chlorpromazine.html Link_out
          PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/chl1441.shtml Link_out
          Wikipedia http://en.wikipedia.org/wiki/Chlorpromazine Link_out
          ATC Codes
          • N05AA01
          AHFS Codes
          • 28:16.08.24
          PDB Entries Not Available
          FDA label Not Available
          MSDS show (75.4 KB)
          Interactions
          Drug Interactions
          Drug Interaction
          Amphetamine Decreased anorexic effect, may increase psychotic symptoms
          Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
          Benzphetamine Antipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
          Bromocriptine The phenothiazine decreases the effect of bromocriptine
          Cisapride Increased risk of cardiotoxicity and arrhythmias
          Dexfenfluramine Decreased anorexic effect, may increase psychotic symptoms.
          Dextroamphetamine Decreased anorexic effect, may increases psychotic symptoms
          Diethylpropion Decreased anorexic effect, may increase psychotic symptoms
          Donepezil Possible antagonism of action
          Fenfluramine Decreased anorexic effect, may increase psychotic symptoms
          Galantamine Possible antagonism of action
          Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
          Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
          Guanethidine Chlorpromazine may decrease the effect of guanethidine.
          Levofloxacin Increased risk of cardiotoxicity and arrhythmias
          Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
          Mazindol Decreased anorexic effect, may increase psychotic symptoms
          Meperidine Increased sedation and hypotension
          Mesoridazine Increased risk of cardiotoxicity and arrhythmias
          Methamphetamine Decreased anorexic effect, may increases psychotic symptoms
          Metrizamide Increased risk of convulsions
          Phendimetrazine Decreased anorexic effect, may increases psychotic symptoms
          Phenmetrazine Decreased anorexic effect, may increase psychotic symptoms
          Phentermine Decreased anorexic effect, may increase psychotic symptoms
          Phenylpropanolamine Decreased anorexic effect, may increase psychotic symptoms
          Pindolol Increased effect of both drugs
          Propranolol Increased effect of both drugs
          Rivastigmine Possible antagonism of action
          Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
          Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Chlorpromazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
          Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
          Tamoxifen Chlorpromazine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Concomitant therapy should be avoided.
          Tamsulosin Chlorpromazine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Chlorpromazine is initiated, discontinued, or dose changed.
          Terbinafine Terbinafine may reduce the metabolism and clearance of Chlorpromazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Chlorpromazine if Terbinafine is initiated, discontinued or dose changed.
          Terfenadine Increased risk of cardiotoxicity and arrhythmias
          Tetrabenazine May cause dopamine deficiency. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
          Thioridazine Increased risk of cardiotoxicity and arrhythmias
          Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
          Tolterodine Chlorpromazine may decrease the metabolism and clearance of Tolterodine. Monitor for adverse/toxic effects of Tolterodine.
          Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
          Tramadol Chlorpromazine may decrease the effect of Tramadol by decreasing active metabolite production.
          Trimethobenzamide Trimethobenzamide and Chlorpromazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
          Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Chlorpromazine, a strong CYP2D6 inhibitor, may also decrease the metabolism and clearance of Trimipramine, a CYP2D6 substrate. Caution should be used during concomitant therapy.
          Triprolidine The antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Chlorpromazine. Monitor for symptoms of ventricular arrhythmias. Additive anticholinergic and CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
          Trospium Trospium and Chlorpromazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
          Venlafaxine Chlorpromazine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Chlorpromazine is initiated, discontinued, or dose changed.
          Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
          Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
          Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Chlorpromazine, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if chlorpromazine is initiated, discontinued or dose changed.
          Food Interactions
          • Avoid alcohol.
          • Take with food to reduce irritation.
          Targets

          1. D(2) dopamine receptor

          Pharmacological action: yes
          Actions: antagonist

          This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

          Organism class: human
          UniProt ID: P14416 Link_out
          Gene: DRD2 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Oades RD, Rao ML, Bender S, Sartory G, Muller BW: Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy. Behav Pharmacol. 2000 Jun;11(3-4):317-30. Pubmed
          2. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. Pubmed
          3. Wu S, Xing Q, Gao R, Li X, Gu N, Feng G, He L: Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci Lett. 2005 Mar 7;376(1):1-4. Epub 2004 Dec 2. Pubmed
          4. Wu SN, Gao R, Xing QH, Li HF, Shen YF, Gu NF, Feng GY, He L: Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients. Acta Pharmacol Sin. 2006 Aug;27(8):966-70. Pubmed
          5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
          6. Seeman P: Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010 Apr;4(1):56-73. Pubmed

          2. D(1A) dopamine receptor

          Pharmacological action: yes
          Actions: antagonist

          This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

          Organism class: human
          UniProt ID: P21728 Link_out
          Gene: DRD1 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Kanba S, Suzuki E, Nomura S, Nakaki T, Yagi G, Asai M, Richelson E: Affinity of neuroleptics for D1 receptor of human brain striatum. J Psychiatry Neurosci. 1994 Jul;19(4):265-9. Pubmed

          3. 5-hydroxytryptamine 2A receptor

          Pharmacological action: yes
          Actions: antagonist

          This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

          Organism class: human
          UniProt ID: P28223 Link_out
          Gene: HTR2A Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Kusumi I, Takahashi Y, Suzuki K, Kameda K, Koyama T: Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain. J Neural Transm. 2000;107(3):295-302. Pubmed
          2. Yamada J, Sugimoto Y, Horisaka K: Serotonin2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibits chlorpromazine- and haloperidol-induced hypothermia in mice. Biol Pharm Bull. 1995 Nov;18(11):1580-3. Pubmed

          4. 5-hydroxytryptamine 1A receptor

          Pharmacological action: yes
          Actions: antagonist

          This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

          Organism class: human
          UniProt ID: P08908 Link_out
          Gene: HTR1A Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Cosi C, Koek W: Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT receptors expressed in HeLa cells. Eur J Pharmacol. 2001 Dec 14;433(1):55-62. Pubmed
          2. Newman-Tancredi A, Gavaudan S, Conte C, Chaput C, Touzard M, Verriele L, Audinot V, Millan MJ: Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. Eur J Pharmacol. 1998 Aug 21;355(2-3):245-56. Pubmed

          5. Alpha-1A adrenergic receptor

          Pharmacological action: yes
          Actions: antagonist

          This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

          Organism class: human
          UniProt ID: P35348 Link_out
          Gene: ADRA1A Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. Pubmed

          6. Alpha-1B adrenergic receptor

          Pharmacological action: yes
          Actions: antagonist

          This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system

          Organism class: human
          UniProt ID: P35368 Link_out
          Gene: ADRA1B Link_out
          Protein Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. Pubmed

          7. Histamine H1 receptor

          Pharmacological action: yes
          Actions: antagonist

          In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

          Organism class: human
          UniProt ID: P35367 Link_out
          Gene: HRH1 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. Pubmed
          2. Church MK, Young KD: The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine. Br J Pharmacol. 1983 Apr;78(4):671-9. Pubmed
          3. Johnson HG, Miller MD: Inhibition of histamine release and ionophore-induced calcium flux in rat mast cells by lidocaine and chlorpromazine. Agents Actions. 1979 Aug;9(3):239-43. Pubmed
          4. Palmer GC, Wagner HR, Palmer SJ, Manian AA: Histamine-, norepinephrine-, and dopamine-sensitive central adenylate cyclases: effects of chlorpromazine derivatives and butaclamol. Arch Int Pharmacodyn Ther. 1978 Jun;233(2):314-25. Pubmed
          5. Ruffolo RR, Patil PN: Kinetics of blockade of different receptors by chlorpromazine in rabbit stomach strips. Eur J Pharmacol. 1978 Mar 15;48(2):151-7. Pubmed
          Enzymes

          1. Cytochrome P450 2D6

          Actions: substrate, inhibitor

          Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

          UniProt ID: P10635 Link_out
          Gene: CYP2D6 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Micallef J, Fakra E, Blin O: [Use of antidepressant drugs in schizophrenic patients with depression] Encephale. 2006 Mar-Apr;32(2 Pt 1):263-9. Pubmed
          2. Otani K, Aoshima T: Pharmacogenetics of classical and new antipsychotic drugs. Ther Drug Monit. 2000 Feb;22(1):118-21. Pubmed
          3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
          4. Yoshii K, Kobayashi K, Tsumuji M, Tani M, Shimada N, Chiba K: Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation of chlorpromazine by human liver microsomes. Life Sci. 2000;67(2):175-84. Pubmed
          5. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. Pubmed
          6. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          2. Cytochrome P450 1A2

          Actions: substrate

          Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

          UniProt ID: P05177 Link_out
          Gene: CYP1A2
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Yoshii K, Kobayashi K, Tsumuji M, Tani M, Shimada N, Chiba K: Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation of chlorpromazine by human liver microsomes. Life Sci. 2000;67(2):175-84. Pubmed
          2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. Pubmed
          3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          3. Cytochrome P450 3A4

          Actions: substrate

          Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

          UniProt ID: P08684 Link_out
          Gene: CYP3A4
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. Pubmed
          2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          4. Cytochrome P450 2E1

          Actions: inhibitor

          Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

          UniProt ID: P05181 Link_out
          Gene: CYP2E1 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. Pubmed
          2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

          5. Cholinesterase

          Actions: inhibitor

          An acylcholine + H(2)O = choline + a carboxylate

          UniProt ID: P06276 Link_out
          Gene: BCHE Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Nasello AG, Gidali D, Felicio LF: A comparative study of the anticholinesterase activity of several antipsychotic agents. Pharmacol Biochem Behav. 2003 Jul;75(4):895-901. Pubmed
          2. Muraoka S, Miura T: Inactivation of cholinesterase induced by chlorpromazine cation radicals. Pharmacol Toxicol. 2003 Feb;92(2):100-4. Pubmed
          3. Spinedi A, Pacini L, Limatola C, Luly P, Farias RN: A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine. Biochem J. 1991 Sep 1;278 ( Pt 2):461-3. Pubmed
          Transporters

          1. Multidrug resistance protein 1

          Actions: substrate, inhibitor

          Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

          UniProt ID: P08183 Link_out
          Gene: ABCB1 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed
          2. Boulton DW, DeVane CL, Liston HL, Markowitz JS: In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci. 2002 May 31;71(2):163-9. Pubmed

          2. Solute carrier family 22 member 1

          Actions: inhibitor

          Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

          UniProt ID: O15245 Link_out
          Gene: SLC22A1 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. Pubmed

          3. Bile salt export pump

          Actions: inhibitor

          Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

          UniProt ID: O95342 Link_out
          Gene: ABCB11 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. Pubmed
          Carriers

          1. Serum albumin

          Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

          UniProt ID: P02768 Link_out
          Gene: ALB Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Kitamura K, Omran AA, Nagata C, Kamijima Y, Tanaka R, Takegami S, Kitade T: Effects of inorganic ions on the binding of triflupromazine and chlorpromazine to bovine serum albumin studied by spectrometric methods. Chem Pharm Bull (Tokyo). 2006 Jul;54(7):972-6. Pubmed
          2. Rukhadze MD, Bezarashvili GS, Sidamonidze NS, Tsagareli SK: Investigation of binding process of chlorpromazine to bovine serum albumin by means of passive and active experiments. Biomed Chromatogr. 2001 Oct;15(6):365-73. Pubmed
          3. Silva D, Cortez CM, Louro SR: Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine and hemin. Braz J Med Biol Res. 2004 Jul;37(7):963-8. Epub 2004 Jun 22. Pubmed
          Comments
          Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19